A novel oral formulation of BIO 300 confers prophylactic radioprotection from acute radiation syndrome in mice

Abstract

Purpose

Exposure to high doses of ionizing radiation can result in hematopoietic acute radiation syndrome (H-ARS) and delayed effects of acute radiation exposure (DEARE). There is no radiation medical countermeasure (MCM) approved by the U.S. Food and Drug Administration which can be used prior to radiation exposure to protect exposed individuals. Different formulations containing synthetic genistein (BIO 300) are being developed to counter the harmful effects of radiation exposure.

Materials and methods

We investigated the efficacy of a BIO 300 oral powder (OP) formulation as a prophylactic radiation MCM against a lethal dose of cobalt-60 gamma-radiation in CD2F1 male mice while comparing to other formulations of BIO 300 and Neulasta (PEGylated filgrastim), a standard of care drug for H-ARS.

Results

BIO 300 OP provided significant radioprotection against ionizing radiation in mice when administered twice per day for six days prior to total-body radiation exposure. Its radioprotective efficacy in the murine model was comparable to the efficacy of a single subcutaneous (sc) injection of Neulasta administered after total-body radiation exposure.

Conclusions

Our results demonstrate that BIO 300 OP, which can be administered orally, is a promising prophylactic radiation countermeasure for H-ARS.

Keywords:

• Animal model
• BIO 300
• mice
• prophylactic
• radiation
• radioprotection

Disclosure statement

The opinions or assertions contained herein are the private views of the authors and are not necessarily those of the Uniformed Services University of the Health Sciences, or the Department of Defense, USA.

Dr. Artur Serebrenik and Dr. Michael D. Kaytor are employees of Humanetics Corporation, Edina, MN, USA. The other authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.

Data availability statement

All data generated or analyzed during this study are included in this article.

Additional information

Funding

This study was supported by funding from Congressionally Directed Medical Research Programs Grant # W81XWH-17-1-0584 awarded to MDK (subawared to VKS by MDK/Humanetics Corporation) and Joint Program Committee-7/Radiation Health Effects Research Program (RHERP) Grant # 1I80 VP00262-01 awarded to VKS and administered by The Henry M. Jackson Foundation for the Advancement of Military Medicine.

Notes on contributors

Vijay K. Singh

Vijay K. Singh, PhD, is a Professor at the School of Medicine/USUHS and a well-recognized radiation biologist involved in the development of promising radiation countermeasures following US FDA Animal Rule. The primary focus of his research is to investigate countermeasures for efficacy, and identify and validate biomarkers for radiation injury and countermeasure efficacy. His research is well-funded by various US government agencies of the Department of Defense and Department of Health and Human Services.

Oluseyi O. Fatanmi

Oluseyi O. Fatanmi, MLS, is a Research Biologist at the Scientific Research Department, AFRRI/USUHS and conducts studies with various radiation countermeasures. He primarily performs and oversees the relevant biochemical, hematologic, microbiological, and immunologic studies to advance radiation medical countermeasures. His focus is to study the effects of radiation injury using various animal models and methodologies to investigate countermeasure efficacy.

Stephen Y. Wise

Stephen Y. Wise, B.Sc., is a Research Associate at the Scientific Research Department, AFRRI/USUHS. His primary focus is to develop promising radiation countermeasures using various animal models to combat radiation injury. His knowledge is focused on the identification of biomarkers, improvement of methodologies, and validation of various biomarkers for the development of radiation countermeasures.

Alana Carpenter

Alana Carpenter, B.Sc., is a Research Assistant at the Scientific Research Department, AFRRI/USUHS. Her primary focus is to investigate countermeasures for efficacy and the identification and validation of various biomarkers for radiation injury and countermeasure efficacy. She is responsible for research data management, quality control and assurance, and interpretation of research data.

Sara Nakamura-Peek

Sara Nakamura-Peek, B.A., is a Research Assistant at the Scientific Research Department, AFRRI/USUHS. Her primary focus of her research is to develop radiation countermeasures. She works with various animal models to identify biomarkers, utilize data to determine efficacy, and interpret data for the study of the effects of radiation injury.

Artur A. Serebrenik

Artur A. Serebrenik, PhD, is a Senior Research and Development Scientist at Humanetics Corporation, Edina, MN, USA.

Michael D. Kaytor

Michael D. Kaytor, PhD, is the Vice President of Research and Development at Humanetics Corporation, Edina, MN, USA.